Intravenous injection of contrast media is required to enhance conspicuity of the vasculature, organs, lesions and tumors in CT, MR, and other imaging modal/ties. Multi-slice/cone-beam spiral CT angiography (CTA) has important and immediate applications in contrast enhanced volumetric and functional imaging for diagnosis of cardiovascular structures, peripheral vessels and solid organs, such as the brain, lung and liver. Synchronization of CT imaging with the propagation of contrast bolus can maximize the signal difference between arteries and background in first-pass studies and may reduce the contrast dose. CT fluoroscopy (CTF) allows real-time tomographic imaging, and has been used to trigger the scan initiation in synchrony with contrast bolus arrival. The overall goal of this project is to develop an adaptive and robust bolus-chasing methodology for multislice/cone-beam spiral CTA in a wide class of diagnostic applications. This will be achieved by instantaneously reconstructing CT images, dynamically predicting bolus propagation using a system identification approach, and adaptively varying scanning pitch from the aortic arch to the feet to allow realtime correction of any significant deviation from the prediction. The specific aims of the R21 Phase are to (1) understand longitudinal bolus propagation characteristics under normal and diseased conditions, and fit the data into an extended Hammerstein model on an individual basis, (2) formulate adaptive and robust control strategies for bolus chasing guided by a patient-specific extended Hammerstein model, and (3) evaluate the performance of the proposed bolus-chasing CTA, and demonstrate its technical feasibility. The specific aims of the R33 phase are to (1)improve multi-slice/cone-beam spiral CT image reconstruction and analysis algorithms for real-time extraction of bolus dynamics, (2) implement and optimize control strategies on a multi-slice/cone-beam CT scanner, and (3) demonstrate the clinical feasibility of bolus-chasing CTA in phantom experiments and patient studies, and characterize its performance. On completion, the optimal imaging and control strategies will have been seamlessly integrated on a multi-slice/cone-beam CT scanner, significantly improved the diagnostic performance of the current CTA, and brought it to the next generation.